A mathematical framework for genetic relatedness analysis involving X chromosome aneuploidies.

The unique features of the X chromosome can be crucial to complement autosomal profiling or to disentangle complex kinship problems, providing in some cases a similar or even greater power than autosomes in paternity/maternity investigations. While theoretical and informatics approaches for pairwise X-linked kinship analyses are well established for euploid individuals, these are still lacking for individuals with an X chromosome aneuploidy. To trigger the fulfilment of this gap, this research presents a mathematical framework that enables the quantification of DNA evidence in pairwise kinship analyses, involving two non-inbred individuals, one of whom with a non-mosaic X chromosome aneuploidy: Trisomy X (47, XXX), Klinefelter (47, XXY) or Turner (45, X0) syndrome. As previously developed for a regular number of chromosomes, this approach relies on the probability of related individuals sharing identical-by-descent (IBD) alleles at one specific locus and it can be applied to any set of independently transmitted markers, with no gametic association in the population. The kinship hypotheses mostly considered in forensic casework are specifically addressed in this work, but the reasoning and procedure can be applied to virtually any pairwise kinship problem under the referred assumptions. Algebraic formulae for joint genotypic probabilities cover all the possible genotypic configurations and pedigrees. Compared with the analyses assuming individuals with a regular number of chromosomes, complicating factors rely on the different possibilities for both the parental origin of the error (either maternal or paternal), and the type of error occurred (either meiotic or post-zygotic mitotic). These imply that a non-inbred female with Triple X or a male with Klinefelter syndrome may carry two IBD alleles at the same locus. Thus, and contrarily to what occurs for the standard case, IBD partitions depend not only on the kinship hypothesis under analysis but also on the genotypic configuration of the analyzed individuals. For some cases, parameters of interest can be inferred, while for others recommended values based on the available literature are provided. This work is the starting point to analyze X-chromosomal data under the scope of kinship problems, involving individuals with aneuploidies, as it will enhance the quantification of the DNA evidence not only in forensics but also in the medical genetics field. We hope it will trigger the development of approaches including other complicating factors, as a greater number of individuals, possibility of the occurrence of mutations and/or silent alleles, as well as the analysis of linked markers.

Microsatellites' mutation modeling through the analysis of the Y-chromosomal transmission: Results of a GHEP-ISFG collaborative study.

The Spanish and Portuguese Speaking Working Group of the International Society for Forensic Genetics (GHEP-ISFG) organized a collaborative study on mutations of Y-chromosomal short tandem repeats (Y-STRs). New data from 2225 father-son duos and data from 44 previously published reports, corresponding to 25,729 duos, were collected and analyzed. Marker-specific mutation rates were estimated for 33 Y-STRs. Although highly dependent on the analyzed marker, mutations compatible with the gain or loss of a single repeat were 23.2 times more likely than those involving a greater number of repeats. Longer alleles (relatively to the modal one) showed to be nearly twice more mutable than the shorter ones. Within the subset of longer alleles, the loss of repeats showed to be nearly twice more likely than the gain. Conversely, shorter alleles showed a symmetrical trend, with repeat gains being twofold more frequent than reductions. A positive correlation between the paternal age and the mutation rate was observed, strengthening previous findings. The results of a machine learning approach, via logistic regression analyses, allowed the establishment of algebraic formulas for estimating the probability of mutation depending on paternal age and allele length for DYS389I, DYS393 and DYS627. Algebraic formulas could also be established considering only the allele length as predictor for DYS19, DYS389I, DYS389II-I, DYS390, DYS391, DYS393, DYS437, DYS439, DYS449, DYS456, DYS458, DYS460, DYS481, DYS518, DYS533, DYS576, DYS626 and DYS627 loci. For the remaining Y-STRs, a lack of statistical significance was observed, probably as a consequence of the small effective size of the subsets available, a common difficulty in the modeling of rare events as is the case of mutations. The amount of data used in the different analyses varied widely, depending on how the data were reported in the publications analyzed. This shows a regrettable waste of produced data, due to inadequate communication of the results, supporting an urgent need of publication guidelines for mutation studies.

Crossing the Wall: Characterization of the Multiheme Cytochromes Involved in the Extracellular Electron Transfer Pathway of Thermincola ferriacetica.

Bioelectrochemical systems (BES) are emerging as a suite of versatile sustainable technologies to produce electricity and added-value compounds from renewable and carbon-neutral sources using electroactive organisms. The incomplete knowledge on the molecular processes that allow electroactive organisms to exchange electrons with electrodes has prevented their real-world implementation. In this manuscript we investigate the extracellular electron transfer processes performed by the thermophilic Gram-positive bacteria belonging to the Thermincola genus, which were found to produce higher levels of current and tolerate higher temperatures in BES than mesophilic Gram-negative bacteria. In our study, three multiheme c-type cytochromes, Tfer_0070, Tfer_0075, and Tfer_1887, proposed to be involved in the extracellular electron transfer pathway of T. ferriacetica, were cloned and over-expressed in E. coli. Tfer_0070 (ImdcA) and Tfer_1887 (PdcA) were purified and biochemically characterized. The electrochemical characterization of these proteins supports a pathway of extracellular electron transfer via these two proteins. By contrast, Tfer_0075 (CwcA) could not be stabilized in solution, in agreement with its proposed insertion in the peptidoglycan wall. However, based on the homology with the outer-membrane cytochrome OmcS, a structural model for CwcA was developed, providing a molecular perspective into the mechanisms of electron transfer across the peptidoglycan layer in Thermincola.